Thermodynamics Research Center / ThermoML | Thermochimica Acta

ABSTRACT

Recrystallization kinetics of amorphous Enzalutamide (two batches prepared by hot-melt extrusion and thermal evaporation of the solvent) was studied by differential scanning calorimetry. The preparation route was found to have significant effect on material thermal stability and initial degree of crystallinity solvent evaporation led to formation of partially crystalline matrix with residual solvent content causing plasticization and the ongoing thermally induced crystallization was largely accelerated. Thermal recrystallization of both Enzalutamide batches led to a similar polymorphic form. The recrystallization kinetics was evaluated by means of modified multivariate kinetic analysis and described in terms of the autocatalytic estak-Berggren and the nth order autocatalytic reaction models. The recrystallization kinetics were found to be dependent on applied heating rate, gradually shifting from the nucleation-growth kinetics to the autocatalyzed 0th order kinetics (with the effective order of reaction changing from 1 to 0.2). The autocatalytic estak-Berggren model appears to be more suitable for predictions of the Enzalutamide recrystallization behavior due to the constancy of the autocatalytic term (M=0.55) with regard to the experimental conditions. In addition, the kinetic predictions of crystallization in pharmaceuticals were discussed in general based on theoretical simulations importance of the aspects influencing the kinetic predictions was demonstrated.